[How are interstitial lung diseases diagnosed in Germany? Results of the scientific registry for the exploration of interstitial lung diseases ("Fibrosis registry") of the WATL]. / Wie werden interstitielle Lungenerkrankungen in Deutschland diagnostiziert? Ergebnisse des wissenschaftlichen Registers zur Erforschung von interstitiellen Lungenerkrankungen ("Fibroseregister") der WATL.

From 1995 to 1999 we evaluated questionnaires sent by pulmonologists and departments of pulmonology in order to register interstitial lung diseases. On the whole 1142 patients (579 males, 563 females, mean age 51.1 +/- 15.3 years, sarcoidosis, n = 511, extrinsic allergic alveolitis, n = 145, idiopathic pulmonary fibrosis, n = 308, bronchiolitis obliterans organizing pneumonia (BOOP), n = 93, others, n = 85) were recorded in the registry. With reference to the mean age sarcoidosis occurred most frequently in the fourth decade and idiopathic pulmonary fibrosis in the sixth decade. In all these diseases bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was predominantly used for further diagnosis. It was striking that high-resolution computed tomography of the thorax was still rarely used when diagnosing these diseases. Apart from the group with BOOP the number of non-smokers in men and women was decisively higher than the average of the population of Germany.

[Fine needle aspiration cytology as diagnostic bed-side method for differential diagnostics of enlarged peripheral lymph nodes]. / Die Feinnadelaspirationszytologie als diagnostische bed-side-Methode zur differenzialdiagnostischen Abklärung peripherer Lymphknotenschwellungen.

Enlarged lymph nodes are a common diagnosis in clinical practice. The causes are varied and both benign or malignant processes might be responsible. Clearly it is important to quickly discern whether the origin is malignant or benign. The aim of this study was to evaluate the reliability and efficacy of aspiration cytology of enlarged lymph nodes. 398 patients with peripheral enlarged lymph nodes, who, in the course of a five-year period, were subjected to at least one immediate cytologic analysis (bed-side-analysis), were included in the study. For comparison the gold standard was defined as either the histological result of a corresponding biopsy or the clinical outcome within an observation period of one year. Cytology analysis reached a sensitivity of 97.6% and a specificity of 96.0% of all lymph nodes analysed. For metastatic lymph nodes of solid neoplasmas (mainly bronchial carcinoma) sensitivity was even 98.7% (90.6% for malignant lymphomas). In conclusion, fine needle lymph node aspiration cytology is a quick, reliable, technically simple method for further assessment of enlarged lymph nodes in order to distinguish between benign and malignant causes. Further differentiation of the underlying type of malignant origin can be achieved with high efficacy. Thus, in the hands of a qualified investigator, fine needle lymph node aspiration cytology is a suitable method for use on a bed-side basis.

[Primary synovial sarcoma of the lung - a rare tumor]. / Primäres Synovialsarkom der Lunge: ein sehr seltener Lungentumor.

We present a 26 year old patient with a primary malignant synovial sarcoma of the lung that was observed for more than one year by a general practitioner and a pulmologist. Finally, because of recurrent hemoptysis a central tumor of mesenchymal origin of the left lower lobe was diagnosed by bronchoscopy. The invasion of the left atrium as far as to the mitral valve was diagnosed by MRT. The patient was operated on by extended pneumonectomy with extracorporeal circulation. The partial excision of the left atrium required plastic reconstruction. In the postoperative course the patient underwent chemo-therapy, 6 cycles adriablastine/ifosfamid. 8 months after the first operation an extensive tumor recurrency occurred with infiltration of the chest wall. The patient refused further radio- or chemotherapy and died 14 months after the operation. Because of the small number of cases therapeutic strategy conceptions do not exist. The resection of the tumor is generally recommended. Chemo- and radiotherapy are accepted as an option for advanced tumor stage.

[Diagnosis and differential diagnosis of bronchial asthma]. / Diagnostik und Differenzialdiagnostik des Asthma bronchiale.

Asthma and COPD (chronic obstructive pulmonary disease) are the most important obstructive pulmonary diseases. Patient's history and physical evaluation give major hints of the underlying disease. Further diagnostic measures comprise lung function analysis including spirometry, plethysmography and--in severe cases--blood gas analysis. Bronchial hyperreactivity may be quantified with an unspecific inhalative provocation test. In many cases allergic diseases are accompanied by asthma. Thus, allergy tests--particularly skin prick tests--have to be carried out. To further define an underlying allergy, in some cases even specific inhalative provocation tests have to be performed. X-ray of the thorax and other imaging techniques, detailed blood analysis, further diagnosis of the upper respiratory tract and the cardiac system may have to be carried out a) to quantify the effects of a severe form of asthma or COPD on other organs, and b) for differential diagnostic examinations.

[Pulmonary aspergillosis in patients without pre-existing pulmonary disease after brain edema prevention with dexamethasone]. / Pulmonale Aspergillose bei Patienten ohne pulmonale Vorerkrankung nach Hirnödem-Prophylaxe mit Dexamethason.

Pulmonary aspergillosis (PA) is a well-described complication in severely immunocompromised hosts. We report on one case of invasive PA and one case of PA following oral dexamethasone prophylaxis for cerebral oedema. Steroids were administered in a dosage of 14 mg and 16 mg, daily respectively for 21 and 15 days. Both patients died despite antifungal treatment. We conclude that PA must be considered as a cause for pulmonary complications in non-immunosuppressed, non-neutropenic patients during oral dexamethasone prophylaxis for neurological disease.

Tumour markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumour marker profiles.

The diagnosis of lung cancer and early knowledge of its histological type are very important; however, this is still a difficult subject for the physician. The aim of this study was to improve the diagnostic efficiency of tumour markers in the diagnosis of bronchial carcinoma by mathematical evaluation of a tumour marker profile employing fuzzy logic modeling. A panel of five tumour markers, including CYFRA 21-1, CEA, NSE, and five additional parameters was determined in 281 patients with confirmed primary diagnosis of bronchial carcinoma of different histology and stage. A further 131 persons, who had acute and chronic benign lung diseases, served as a control group. A classificator was developed using a fuzzy-logic rule-based system. The diagnostic value of the combined tumour markers was significantly better than that of the individual markers and of a combination of CYFRA 21-1, CEA, and NSE. The discrimination of malignant vs benign diseases was realized with a sensitivity of 87.5% and specificity of 85.5%. The rate of correct classification of small-cell vs non-small-cell lung carcinoma was 90.6% and 91.1%, respectively; for squamous cell carcinoma vs adenocarcinoma it was 76.8% and 78.8%, respectively. Our detailed analysis has shown that the fuzzy logic system improves diagnostic accuracy up to a rate of 20%, especially in early stages and in patients with all marker levels in the grey area. Our concept proved to be more powerful than measurement of single markers or the combination of CEA, CYFRA 21-1, and NSE. Its use may help in distinguishing between malignant and benign disease and make it possible to define different subgroups of patients earlier in the course of their disease.

[Immunoglobulin content in bronchoalveolar lavage fluid in sarcoidosis]. / Untersuchungen zum Immunglobulingehalt in der broncho-alveolären Lavage bei Sarkoidose.

The amount of albumins and immunoglobulins in the broncho-alveolar lavage fluid of sarcoidosis patients were measured and correlated with cellular activity parameters in sarcoidosis. It could be shown that IgG and IgA, related to albumin, were increased in comparison with serum while the IgM fraction was decreased. In general, the highest values of immunoglobulins were found in active sarcoidosis.

[Bronchoalveolar lavage in patients with sarcoidosis--methodologic aspects of the collection, immunologic characterization of lymphocytes and studies of immunoglobulin content]. / Broncho-alveoläre Lavage bei Sarkoidosepatienten--Methodische Aspekte der Gewinnung, immunologische Charakterisierung von Lymphozyten und Untersuchungen zum Immunglobulingehalt.

The activity of alveolitis in 25 patients with pulmonary sarcoidosis was determined by analysis of T-Lymphocytes and their subpopulations collected by broncho-alveolar lavage. The characterization of the lymphocytes was performed with monoclonal antibodies (BL-series). An amount of T-lymphocytes higher than 28% of all cells and a proportion of T4/T8-lymphocytes of 8:1 and over are signs of the activity of the alveolitis and an indication for corticoid therapy.

[Value of cytologic diagnosis of pulmonary carcinoid tumors. A morphologico-clinical analysis]. / Zur Wertigkeit der zytologischen Diagnostik von pulmonalen Karzinoidtumoren. Eine morphologisch-klinische Analyse.

14 centrally and 16 peripherally located carcinoid tumors of the lung were included in the study. For the centrally situated carcinoids the cytological interpretation of imprints or smears from the surface of the biopsy specimens turned out to be superior to the histological diagnosis based on the same endoscopic bronchial biopsy. 10 out of 12 cytologically investigated cases were correctly diagnosed. In the remaining 2 cases one was misdiagnosed as a small cell carcinoma and the other one raised suspicion of malignancy (Pap-III-finding), but no definitive diagnosis could be made. By contrast, out of 11 histologically investigated endoscopic biopsies from central carcinoids 5 were misdiagnosed as small cell carcinomas and in one case the material obtained endoscopically was inadequate. Out of the 16 peripheral carcinoid tumors only 5 were diagnosed cytologically: 3 by catheter aspiration and 2 by transthoracic needle biopsy. The characteristic cytologic feature of carcinoid tumors and the cytological differential diagnosis are described in detail.

[Results of the transthoracic fine needle biopsy]. / Ergebnisse der transthorakalen Feinnadelbiopsie.

The transthoracic fine needle biopsy is a very efficient method in the differential diagnosis of pathological intraplumonary or mediastinal processes. If the material is representative (out of 918 patients in 71.6 percent), the cytological examination produced a correct result in 93.4 percent (in 614 cases out of 658). In 428 cases of intrathoracic malignant diseases an accurate diagnosis was established in 94.6 percent, and out of the patients with a benign inflammatory disease we could give frequently a hint at the definitive diagnosis in addition with other clinical and paraclinical dates. The false positive rate was 1.3 percent, and in 5.3 percent a false negative result was obtained. Our rate of complications was 16.7 percent.

[The bioptical exploration of non-tuberculous cavities in the lungs]. / Zur bioptischen Exploration von nichttuberkulösen Höhlen im Bereich der Lunge.

Considering the difficulties in X-ray differentiating, every lung abscess should be submitted to a bronchologic-bioptical control. In using the fine needle biopsy for the cytological evaluation, no severe complications could be observed so far. A promising therapy of the lung abscess is given by perthoracal local treatment.

[Biopsy of suspected metastatic lung lesions]. / Biopsie metastasenverdächtiger Lungenherde.

Among the tumours of the lung metastatic formations are to be expected in 7.5 to 10% of the cases. This is based on the anamnesis, on the X-ray findings or on the results from bioptical examinations. Compared with primary tumours, cytological investigations of the exfoliative material are less effective (positive results in about 50% of the cases). As metastatic formations primarily manifest themselves in the interstitium and only late touch the bronchial system, direct excision of material or methods of puncture respectively are from the first much more promising. Sixty out of 95 patients with pulmonary processes, supposed to show metastatic formations, had been submitted to a bioptical control, mainly by means of fine needle biopsy, with the following cytological evaluation of the material. In 50 cases it was possible to secure the finding morphologically, i.e. in 83.3% of the cases. The cytological appearance, too, leads to a clear position to the primary tumour, for example in hypernephroid carcinomas, pigment-storing melanomas, diseases of the lymphatic system and various sarcomas.

[Studies on the E rosette test (author's transl)]. / Untersuchungen zum E-Rosettentest.

The number of T lymphocytes in the peripheral blood of normal subjects and patients with bronchial carcinoma was determined by using the E rosette test. In a comparative study we counted the "total" rosette forming cells and the "active" rosette forming cells using a lymphocytes-sheep red cells-ratio (Ly-SRBC-R) of 1:8 and 1:40. The numbers or rosettes in the two test systems are in correlation with the Ly-SRBC-R despite other differences in the techniques. -A significant difference was determined between normal subjects and patients with the "active" rosette test only with a L-SRBC-R of 1:40. By contrast the values with the L-SRBC-R of 1:8 were not very different between the two groups. -Also the number of "total" rosettes was significantly different between blood donors and carcinoma patients, using the L-SRBC-R. 1:40. -These results are not of direct clinical relevance, because the values of normal subjects and carcinoma patients are overlapping.

Effects of amphotericin B and its methyl ester on the antiviral activity of polyinosinic:polycytidylic acid.

Since the macrolide polyene antibiotics, amphotericin B (AmB) and its methyl ester (AmBME), augment interferon production by polyriboinosinic:polyribocytidylic acid [poly(I):poly(C)] in vitro, experiments were undertaken to determine how AmB and AmBME affect the antiviral activity of poly(I):poly(C) and interferon. AmBME increased the direct antiviral activity of poly(I):poly(C) 10(2)-to 10(4)-fold in L929, Flow 6000, and T98G cells. Viral replication, measured by either direct plaque formation or virus yield, was markedly reduced. Serum interferon levels in mice induced by poly(I):poly(C) were enhanced by concomitant treatment with AmB. However, the therapeutic effects of poly(I):poly(C) in encephalomyocarditis and Semliki Forest virus infections were not augmented by combined treatment with poly(I):poly(C) and AmB. In vitro, the antiviral effects of exogenous interferon were markedly inhibited by AmB and AmBME. This inhibition may have contributed to the adverse effects of the macrolide polyenes in encephalomyocarditis and Semliki Forest virus infections in vivo. These findings further substantiate the effectiveness of macrolide polyenes in augmenting cellular penetration of macromolecules. However, therapeutic application may be limited by the complex interactions which occur between compounds administered in vivo.

[Cytodiagnosis in lung diseases]. / Zytodiagnostik bei Lungenkrankheiten.

The main application of the clinical cytology in pulmonary diseases is a possibly early and certain tumour diagnostics. This is successful in 80 to 90% of the cases. The rate of the falsely positive findings is in general lower than 1%, in the own material at 0.5%. When the cytodiagnostician taken into consideration reference pictures to benign diseases and helps his clinical partner in the classification of these findings into the entire clinical pictures, the value of the cytodiagnostics increases manifold. These descriptions were confirmed by cytological pictures and of cases instances.

Mechanistic studies of polyene enhancement of interferon production by polyriboinosinic-polyribocytidylic acid.

The production of interferon by polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-diethylaminoethyl-dextran in L929 cells was enhanced from 10 to 100 times by polyene macrolides, including amphotericin B (AmB), AmB methyl ester, nystatin, and filipin. AmB and its water-soluble methyl ester were the most effective; retinol, a nonmacrolide polyene, was ineffective. Interferon induction by Newcastle disease virus was not enhanced by AmB. The kinetics of interferon production were not markedly altered by AmB. Polyenes and poly(I) . poly(C)-diethylaminoethyl-dextran did not need to be present on cells simultaneously to enhance interferon production. Pretreatment with polyenes was as effective as simultaneous addition. Even treatment of washed cells, several hours after removal of poly(I) . poly(C)-diethylaminoethyl-dextran, resulted in enhancement of interferon production. AmB did not appear to form a macromolecular complex with poly(I) . poly(C) in that neither the ultraviolet absorption spectrum nor the melting point of poly(I) . poly(C) was altered by mixing with AmB. Isotopic studies indicated that AmB did not enhance binding of poly(I) . poly(C) to cells. Since the macrolide polyenes have been demonstrated to bind to cell membrane sterols with subsequent alterations in membrane permeability barriers, they may enhance interferon production by increasing cell penetration of poly(I) . poly(C).